Alveolar macrophages (AM) are unique among macrophages in their mitotic potential, use of aerobic metabolism during phagocytosis, and pattern of immunoregulatory function. The factors leading to such specialization are poorly understood. These cells are embedded within surfactant and surfactant affects both effector and immunoregulatory functions of AM. Determination of the mechanisms by which surfactant alters AM function will require scrutiny of the biochemical events occurring during interaction of surfactant and cells. These studies focus on the effect of surfactant on suppressive activities of AM and will test the following hypotheses: surfactant binds to AM via specific surface apoprotein receptors and is distributed to lysosomes where enzymatic reactions lead to its metabolism to amino acids and fatty acids; binding, uptake and/or metabolism of surfactant by human AM contributes to the immunosuppressive activity of AM through the following: a.) enhancement of inhibition by plasma membranes, b.) production of oxidized lipids which are inhibitory, c.) and/or mediators. The hypotheses will be tested according to the following Specific Aims: 1.) to determine the in vitro binding and kinetics of uptake of surfactant by rat AM; 2.) to determine the cellular distribution of surfactant and dipalmitoyl phosphatidylcholine (DPPC) after uptake by rat AM; 3.) to determine the metabolic fate of surfactant after uptake by rat AM and the concomitant release of immunologically active mediators; and 4.) to examine the relationships between surfactant metabolism by human AM and immunoregulation by human AM of lymphocyte response to soluble stimuli. The long- term goal is to apply these findings to disease. Methodology includes cellular immunology (lymphocyte blastogenesis, assay of interleukin-1 activity, enzyme-linked immunoassay) and biochemistry (enzyme assays, assay of 125 Iodine binding and uptake, subcellular fractionation, electrophoresis, lipid analysis).

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Physician Scientist Award (K11)
Project #
5K11HL001829-03
Application #
3087392
Study Section
Research Manpower Review Committee (MR)
Project Start
1987-09-30
Project End
1992-09-29
Budget Start
1989-09-30
Budget End
1990-09-29
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
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